| Objective:The present study was designed to establish and validate the methodology of methotrexate(MTX) determination in whole blood, to evaluate the relationship between serum concentration of MTX and adverse reactions,the affection of calcium folinate(CF) rescue to plasma MTX concentration and side effects during high-dose methotrexate(HD-MTX) treatment in children with acute lymphoblastic leukemia(ALL).Methods:Plasma samples were collected after24-h infusions of MTX in133children and subsequently analyzed by flurescence polarization immunoassay(FPIA) to determine the MTX concentrations. Data about clinical character, Plasma MTX concentration and side effects were recorded during the course of treatment.Results:All MTX assay calibration curve meet the following criteria Polarization Error(PERR) is-3.00to+3.00for all calibrators; Root mean squared error(RMSE) less than or equal to3.00;A11controls are within the acceptable range.There were some relationship between the plasma MTX concentration, side effects and uric acid(UA). By comparison, The UA in Level I concentration has a significant difference (male:(191.6±66.3)vs(226.1±74.5) μmol/L, P<0.05; female:(185.2±14.9)vs(226.1±74.5) μmol/L, P<0.05)。The UA in Level0side effects has a significant difference (184.9±45.9vs226.1±74.5, P<0.05). We should pay more attention to the patients who were younger and shorter。 By investigation the MTX concentration and it’s side effects, we found the incidence and level of side effects was lower when the MTX concentration less than or equal to0.01μmol/L.。Oral mucositis, vomiting, elevated liver enzymes were the major side effects。Severe renal toxicity, infection and shin disesse were significantly related to a high plasma MTX concentration. MTX-induced toxicity did not increase though delaying the rescue to42hr and decreasing the dose of CF.Conclusion:The results indicate that FPIA is a specific and simple method when tracing the MTX concentration. The toxic effects of MTX are minor when the concentration drop to<0.3μmol/L in48hr though CF rescue is discontinued. While there are some individual difference between the patients。To the children who were younger and shorter, the toxic effects of MTX may occur when the MTX concentration is low. But to older or taller children, the toxic effects of MTX can not happen at the same concentration. When the concentration of MTX surpass a limit, the relationship between the MTX concentration, the incidence and the level of side effect were not so significant. We should determined the dose of CF according to the MTX concentration so as to improve the efficiency and safety of HD-MTX. |
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